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Integrated Single Cell Analysis of Human Lung Fibrosis Resolves Cellular Origins of Predictive Protein Signatures in Body Fluids

30 Pages Posted: 20 Feb 2020 Publication Status: Review Complete

See all articles by Christoph H. Mayr

Christoph H. Mayr

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Lukas M. Simon

Helmholtz Zentrum München - Institute of Computational Biology

Gabriela Leuschner

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Meshal Ansari

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Philipp E. Geyer

Max Planck Institute for Biochemistry - Department of Proteomics and Signal Transduction

Ilias Angelidis

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Maximilian Strunz

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Pawandepp Singh

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Nikolaus Kneidinger

Ludwig Maximilian University of Munich (LMU) - Department of Internal Medicine V

Frank Reichenberger

Asklepios Fachkliniken Munich-Gauting

Edith Silbernagel

Asklepios Fachkliniken Munich-Gauting

Stephan Böhm

Ludwig Maximilian University of Munich (LMU) - Max von Pettenkofer-Institute

Heiko Adler

Helmholtz Zentrum München - German Center for Lung Research (DZL)

Anne Hilgendorff

Ludwig Maximilian University of Munich (LMU) - Department of Neonatology

Michael Lindner

Asklepios Fachkliniken Munich-Gauting

Antje Prasse

Hannover Medical School - Department of Pneumology

Jürgen Behr

Ludwig Maximilian University of Munich (LMU) - Department of Internal Medicine V

Matthias Mann

Max Planck Institute for Biochemistry - Department of Proteomics and Signal Transduction; University of Copenhagen

Oliver Eickelberg

University of Colorado at Denver - Division of Respiratory Sciences and Critical Care Medicine

Fabian J. Theis

Technische Universität München (TUM); Helmholtz Zentrum München - Institute of Computational Biology

Herbert B. Schiller

Helmholtz Zentrum München - German Center for Lung Research (DZL)

More...

Abstract

Single cell genomics enables characterization of disease specific cell states, while improvements in mass spectrometry bring the clinical use of body fluid proteomics within reach. The correspondence of cell state changes in diseased organs to peripheral protein signatures is currently unknown. Here, we leverage single-cell RNA-seq and proteomic analysis of large pulmonary fibrosis patient cohorts to identify disease specific changes on the cellular level and their corresponding reflection in body fluid proteomes. We discovered and validated transcriptional changes in 45 cell types across three patient cohorts that translated into distinct changes in bronchoalveolar lavage fluid and plasma proteomes. These protein signatures correlated with diagnosis, lung function, smoking and injury status. Specifically, the altered expression of a novel marker of lung health, CRTAC1, in alveolar epithelium is robustly reflected in patient plasma. Our findings have direct implications for future non-invasive prediction and monitoring of pathological cell state changes in patient organs.

Keywords: fibrosis, systems medicine, single cell RNA-seq, proteomics, data integration, biomarker

Suggested Citation

Mayr, Christoph H. and Simon, Lukas M. and Leuschner, Gabriela and Ansari, Meshal and Geyer, Philipp E. and Angelidis, Ilias and Strunz, Maximilian and Singh, Pawandepp and Kneidinger, Nikolaus and Reichenberger, Frank and Silbernagel, Edith and Böhm, Stephan and Adler, Heiko and Hilgendorff, Anne and Lindner, Michael and Prasse, Antje and Behr, Jürgen and Mann, Matthias and Eickelberg, Oliver and Theis, Fabian J. and Schiller, Herbert B., Integrated Single Cell Analysis of Human Lung Fibrosis Resolves Cellular Origins of Predictive Protein Signatures in Body Fluids. Available at SSRN: https://ssrn.com/abstract=3538700 or http://dx.doi.org/10.2139/ssrn.3538700
This version of the paper has not been formally peer reviewed.

Christoph H. Mayr

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Lukas M. Simon

Helmholtz Zentrum München - Institute of Computational Biology ( email )

Germany

Gabriela Leuschner

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Meshal Ansari

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Philipp E. Geyer

Max Planck Institute for Biochemistry - Department of Proteomics and Signal Transduction

Germany

Ilias Angelidis

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Maximilian Strunz

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Pawandepp Singh

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Nikolaus Kneidinger

Ludwig Maximilian University of Munich (LMU) - Department of Internal Medicine V ( email )

Germany

Frank Reichenberger

Asklepios Fachkliniken Munich-Gauting

Germany

Edith Silbernagel

Asklepios Fachkliniken Munich-Gauting

Germany

Stephan Böhm

Ludwig Maximilian University of Munich (LMU) - Max von Pettenkofer-Institute

Pettenkoferstraße 9A
München, 80336
Germany

Heiko Adler

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

Anne Hilgendorff

Ludwig Maximilian University of Munich (LMU) - Department of Neonatology ( email )

Germany

Michael Lindner

Asklepios Fachkliniken Munich-Gauting

Germany

Antje Prasse

Hannover Medical School - Department of Pneumology ( email )

Germany

Jürgen Behr

Ludwig Maximilian University of Munich (LMU) - Department of Internal Medicine V ( email )

Germany

Matthias Mann

Max Planck Institute for Biochemistry - Department of Proteomics and Signal Transduction

Germany

University of Copenhagen

Nørregade 10
Copenhagen, København DK-1165
Denmark

Oliver Eickelberg

University of Colorado at Denver - Division of Respiratory Sciences and Critical Care Medicine ( email )

United States

Fabian J. Theis

Technische Universität München (TUM) ( email )

Arcisstrasse 21
Munich, DE 80333
Germany

Helmholtz Zentrum München - Institute of Computational Biology

Germany

Herbert B. Schiller (Contact Author)

Helmholtz Zentrum München - German Center for Lung Research (DZL) ( email )

Germany

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